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Programmed Necrosis in Host Defense
1Robert W. Woodruff Professor Emeritus, Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, 30322, USA. mocarski@stanford.edu.
Current Topics in Microbiology and Immunology
|August 10, 2023
Summary
Mammalian cells use cell death pathways like apoptosis and necroptosis to fight viral infections. Viruses counter these defenses, but Z-nucleic acid sensor ZBP1 plays a key role in recognizing viral threats.
Area of Science:
- Immunology
- Cell Biology
- Virology
Background:
- Host immune systems rely on cellular defense mechanisms to combat infectious diseases.
- Pathogens evolve strategies to evade or suppress host immune responses, including cell death pathways.
- Cell autonomous signaling pathways initiate inflammatory responses, deploy restriction factors, and induce cell death upon pathogen invasion.
Purpose of the Study:
- To explore the intricate interplay between viruses and host cell death machinery.
- To highlight the role of programmed cell death pathways in controlling viral infections.
- To emphasize the significance of Z-nucleic acid sensor ZBP1 in detecting viral pathogens.
Main Methods:
- Review of established and emerging literature on host-pathogen interactions and cell death.
- Analysis of signaling pathways involved in apoptosis and necroptosis.
- Investigation of viral strategies to inhibit host cell death mechanisms.
Main Results:
- Diverse cell death pathways, including apoptosis and necroptosis, are crucial for early control of viral infections.
- Activation of death receptors (DRs), toll-like receptors (TLRs), or Z-nucleic acid binding protein 1 (ZBP1) can trigger apoptosis or necroptosis.
- Viruses, such as herpesviruses and poxviruses, encode suppressors to block these host cell death pathways.
Conclusions:
- Z-nucleic acid sensor ZBP1 is vital for the cell autonomous recognition of DNA and RNA virus infections.
- Understanding the 'detente' between viruses and host cell death machinery is key to controlling viral spread.
- Targeting viral suppression of cell death pathways offers potential therapeutic strategies against viral diseases.
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